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The development of a robust light source that emits one photon at a time will allow new technologies such as secure communication through quantum cryptography. Devices based on fluorescent dye molecules, quantum dots and carbon nanotubes have been demonstrated, but none has combined a high single-photon flux with stable, room-temperature operation. Luminescent centres in diamond have recently emerged as a stable alternative, and, in the case of nitrogen-vacancy centres, offer spin quantum bits with optical readout. However, these luminescent centres in bulk diamond crystals have the disadvantage of low photon out-coupling. Here, we demonstrate a single-photon source composed of a nitrogen-vacancy centre in a diamond nanowire, which produces ten times greater flux than bulk diamond devices, while using ten times less power. This result enables a new class of devices for photonic and quantum information processing based on nanostructured diamond, and could have a broader impact in nanoelectromechanical systems, sensing and scanning probe microscopy.

Eukaryotic cells coordinately control anabolic and catabolic processes to maintain cell and tissue homeostasis. The mechanistic target of rapamycin complex 1 (mTORC1) promotes nutrient-consuming anabolic processes, such as protein synthesis1. Here, we show that accompanying an increase in protein synthesis, mTORC1 activation also promotes an increased capacity for protein degradation. Cells with activated mTORC1 exhibited elevated levels of intact and active proteasomes through a global increase in the expression of genes encoding proteasome subunits. The increase in proteasome gene expression, cellular proteasome content, and rates of protein turnover downstream of mTORC1 were all dependent on induction of the transcription factor nuclear factor erythroid-derived 2-related factor 1 (NFE2L1 or NRF1). Genetic activation of mTORC1 through loss of the tuberous sclerosis complex tumor suppressors or physiological activation of mTORC1 in response to growth factors or feeding resulted in increased NRF1 expression in cells and tissues. We find that this NRF1-dependent elevation of proteasome levels serves to increase the intracellular pool of amino acids, which thereby influences rates of new protein synthesis. Therefore, mTORC1 signaling increases the efficiency of proteasome-mediated protein degradation for both quality control and as a mechanism to supply substrate for sustained protein synthesis.

Graphene-based metamaterials have been theoretically demonstrated as an enabler for applications as perfect absorbers, photodetectors, light emitters, modulators, and tunable spintronic devices. However, challenges associated with conventional film deposition techniques have made the multilayered metamaterial difficult to fabricate, which have severely limited experimental validations. Herein, the experimental demonstration of the phototunable graphene-based multilayered metamaterials on diverse substrates by a transfer-free, solution-phase deposition method is presented. The optical properties of the metamaterials are tuned dynamically by controllable laser-mediated conversion from graphene oxide layers into graphene counterparts, which exhibit different degrees of conversion, which would offer huge potential for devices design and fabrication. The converted graphene layers present comparable (within 10%) optical conductivity to their chemical vapor deposited analogues. Moreover, laser patterning leads to functional photonic devices such as ultrathin flat lenses embedded in the lab-on-chip device, which maintains consistency and exhibits subwavelength focusing resolution in aqueous environments without any noticeable degradation compared with the original lens. This graphene-based metamaterial provides a new experimental platform for broad applications in on-chip integrated photonic, biomedical, and microfluidic devices.

Understanding how nanoparticles are eliminated from the body is required for their successful clinical translation. Many promising nanoparticle formulations for in vivo medical applications are large (>5.5 nm) and nonbiodegradable, so they cannot be eliminated renally. A proposed pathway for these nanoparticles is hepatobiliary elimination, but their transport has not been well-studied. Here, we explored the barriers that determined the elimination of nanoparticles through the hepatobiliary route. The route of hepatobiliary elimination is usually through the following pathway: (1) liver sinusoid, (2) space of Disse, (3) hepatocytes, (4) bile ducts, (5) intestines, and (6) out of the body. We discovered that the interaction of nanoparticles with liver nonparenchymal cells (e.g., Kupffer cells and liver sinusoidal endothelial cells) determines the elimination fate. Each step in the route contains cells that can sequester and chemically or physically alter the nanoparticles, which influences their fecal elimination. We showed that the removal of Kupffer cells increased fecal elimination by >10 times. Combining our results with those of prior studies, we can start to build a systematic view of nanoparticle elimination pathways as it relates to particle size and other design parameters. This is critical to engineering medically useful and translatable nanotechnologies.

Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role of this protein kinase complex in cancer is not well understood. Through an integrated analysis of cell lines, in vivo models and clinical samples, we demonstrate that mTORC2 is frequently activated in glioblastoma (GBM), the most common malignant primary brain tumor of adults. We show that the common activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates mTORC2 kinase activity, which is partially suppressed by PTEN. mTORC2 signaling promotes GBM growth and survival, and activates NF-κB. Importantly, this mTORC2-NF-κB pathway renders GBM cells and tumors resistant to chemotherapy in a manner independent of Akt. These results highlight the critical role of mTORC2 in GBM pathogenesis, including through activation of NF-κB downstream of mutant EGFR, leading to a previously unrecognized function in cancer chemotherapy resistance. These findings suggest that therapeutic strategies targeting mTORC2, alone or in combination with chemotherapy, will be effective in cancer.

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